{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:41Z","timestamp":1792088021640,"version":"4.4.0"},"reference-count":36,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council"},{"name":"King's College London"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The tympanic membrane (i.e. eardrum) sits at the interface between the middle and external ear. The tympanic membrane is composed of three layers: an outer ectoderm-derived layer, a middle neural crest-derived fibroblast layer with contribution from the mesoderm-derived vasculature, and an inner endoderm-derived mucosal layer. These layers form a thin sandwich that is often perforated following trauma, pressure changes or middle ear inflammation. During healing, cells need to bridge the perforation in the absence of an initial scaffold. Here, we assessed the contribution, timing and interaction of the different layers during membrane repair by using markers and reporter mice. We showed that the ectodermal layer is retracted after perforation, before proliferating away from the wound edge, with keratin 5 basal cells migrating over the hole to bridge the gap. The mesenchymal and mucosal layers then used this scaffold to complete the repair, followed by advancement of the vasculature. Finally, differentiation of the epithelium led to formation of a scab. Our results reveal the dynamics and interconnections between the embryonic germ layers during repair and highlight how defects might occur.<\/jats:p>","DOI":"10.1242\/dmm.050466","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T04:56:05Z","timestamp":1708664165000},"source":"Crossref","is-referenced-by-count":8,"title":["Tracking cell layer contribution during repair of the tympanic membrane"],"prefix":"10.1242","volume":"17","author":[{"given":"Olivia M.","family":"Dinwoodie","sequence":"first","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology , Faculty of Dentistry, Oral and Craniofacial Sciences , , London SE1 9RT , UK"},{"name":"King's College London , Faculty of Dentistry, Oral and Craniofacial Sciences , , London SE1 9RT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8871-6094","authenticated-orcid":false,"given":"Abigail S.","family":"Tucker","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology , Faculty of Dentistry, Oral and Craniofacial Sciences , , London SE1 9RT , UK"},{"name":"King's College London , Faculty of Dentistry, Oral and Craniofacial Sciences , , London SE1 9RT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-1989","authenticated-orcid":false,"given":"Juan M.","family":"Fons","sequence":"additional","affiliation":[{"name":"Centre for Craniofacial and Regenerative Biology , Faculty of Dentistry, Oral and Craniofacial Sciences , , London SE1 9RT , UK"},{"name":"King's College London , Faculty of Dentistry, Oral and Craniofacial Sciences , , London SE1 9RT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"2024040210562838100_DMM050466C1","doi-asserted-by":"publisher","first-page":"962040","DOI":"10.3389\/fbioe.2022.962040","article-title":"Endothelial cells during craniofacial development: populating and patterning the head","volume":"29","author":"Asrar","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2024040210562838100_DMM050466C2","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1242\/dev.127.8.1671","article-title":"Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis","volume":"127","author":"Chai","year":"2000","journal-title":"Development"},{"key":"2024040210562838100_DMM050466C3","doi-asserted-by":"publisher","first-page":"E160","DOI":"10.1097\/MAO.0000000000002060","article-title":"Cellular dynamics in early healing of mouse tympanic membranes","volume":"40","author":"Chari","year":"2019","journal-title":"Otol. 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Otorhinolaryngol."},{"key":"2024040210562838100_DMM050466C6","author":"Dolhi","year":"2023"},{"key":"2024040210562838100_DMM050466C7","doi-asserted-by":"publisher","first-page":"3471","DOI":"10.1016\/j.bbamcr.2013.06.010","article-title":"Cell death by cornification","volume":"1833","author":"Eckhart","year":"2013","journal-title":"Biochim. Biophys Acta Mol. 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Genet."},{"key":"2024040210562838100_DMM050466C10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.stem.2020.10.006","article-title":"A hierarchy of proliferative and migratory keratinocytes maintains the tympanic membrane","volume":"28","author":"Frumm","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2024040210562838100_DMM050466C11","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/S0030-6665(20)30467-9","article-title":"Tympanic membrane wound healing: an overview [Article]","volume":"28","author":"Gladstone","year":"1995","journal-title":"Otolaryngol. Clin. North Am."},{"key":"2024040210562838100_DMM050466C12","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1097\/00129492-200305000-00004","article-title":"The effects of Hyaluronic acid, epidermal growth factor, and mitomycin in an experimental model of acute traumatic tympanic membrane perforation [Article]","volume":"24","author":"G\u00fcneri","year":"2003","journal-title":"Otol. Neurotol."},{"key":"2024040210562838100_DMM050466C34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010092","article-title":"The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis","volume":"19","author":"Hirayama","year":"2017","journal-title":"Int. J. Mol. 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Neurotol."},{"key":"2024040210562838100_DMM050466C15","first-page":"101","article-title":"Structure and function of the tympanic membrane: a review","volume":"49","author":"Lim","year":"1995","journal-title":"Acta Oto-Rhino-Laryngologica Belgica"},{"key":"2024040210562838100_DMM050466C16","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1006\/dbio.2001.0154","article-title":"Formation of the middle ear: recent progress on the developmental and molecular mechanisms","volume":"231","author":"Mallo","year":"2001","journal-title":"Dev. 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